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Exercise dose and metformin for vascular health in adults with metabolic syndrome

运动剂量和二甲双胍对代谢综合征成人血管健康的影响

基本信息

批准号：
9239977
负责人：
Steven K Malin
金额：
$ 73.97万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-01 至 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9239977
关键词：
Accelerometer Address Adherence Adult Aerobic Exercise Affect Attenuated Behavior Blood Glucose Blood Pressure Blood Vessels Carbohydrates Cardiovascular system Cause of Death Clinical Closure by clamp Diabetes Mellitus Disease Dose Double-Blind Method Double-blind trial Drug Interactions Early treatment Etiology Euglycemic Clamping Exercise Exercise Therapy Fasting Functional disorder Future Glucose Glycosylated hemoglobin A Goals Health Healthcare Hyperglycemia Hypertension Indirect Calorimetry Inflammation Insulin Insulin Resistance Intervention Knowledge Measures Mediating Metabolic Metabolic syndrome Metformin Microcirculation Mitochondria Morbidity - disease rate Muscle Cells Nitric Oxide Non-Insulin-Dependent Diabetes Mellitus OGTT Obesity Outcome Oxidative Stress Patients Pattern Perception Peripheral Pharmaceutical Preparations Pharmacology Physical activity Physiologic pulse Placebos Pre-Post Tests Public Health Quality of life Randomized Recommendation Resistance Role Signal Transduction Skeletal Muscle Testing Therapeutic Training Trees Ultrasonography Vascular Diseases Work arterial stiffness arteriole base cardiovascular health contrast enhanced disorder prevention disorder risk endothelial dysfunction exercise adherence exercise intensity exercise training glucose disposal glucose tolerance glycemic control health organization improved indexing insight insulin sensitivity middle age mortality oxidation post intervention prevent sedentary lifestyle treatment effect trend trial design

项目摘要

PROJECT SUMMARY/ABSTRACT Arterial disease is the leading cause of morbidity/mortality in Metabolic syndrome (MetS). This occurs early as evidenced by arterial dysfunction that, in turn, raises blood pressure and glucose. Health organizations recommend exercise in an intensity based manner to promote cardiovascular adaptation and prevent disease. Metformin is a common anti-diabetes medication that reduces future type 2 diabetes and CVD risk. However, the optimal exercise dose to be combined with metformin for additive effects on vascular function is unknown. Based on our preliminary work, our overall hypothesis is that metformin blunts adaptation following high intensity exercise training (HiEx) by lowering mitochondrial derived oxidative stress signaling. We further hypothesize that low intensity exercise (LoEx) training combined with metformin will promote additive effects on vascular function compared to LoEx or HiEx+metformin, and maintain/improve non-exercise physical activity patterns. In this double-blind trial, obese 30-60y MetS patients will be randomized to: 1) LoEx+placebo; 2) LoEx+metformin, 3) HiEx+placebo; or 4) HiEx+metformin for 16 weeks. We will evaluate measures of arterial stiffness (pulse wave velocity and augmentation index), and nitric oxide-mediated arterial function in conduit (flow mediated dilation), resistance (post-ischemic flow velocity) and microvascular (contrast enhanced ultrasound) vessels, before and during a euglycemic clamp pre and post intervention (AIM 1). We will also assess 24 hr blood pressure as well as determine skeletal muscle metabolic insulin resistance and glucose tolerance (AIM 2) to address clinical and experimental questions related to health care. Further, we will examine the effect of metformin on exercise adherence, non-exercise physical activity and quality of life during the 16 week intervention as well as during an 8 week “free-living” period (Exploratory AIM 3) to improve public health physical activity recommendations when co-prescribed medication. If these hypothesis are correct, they will indicate 1) whether and how metformin should be combined with physical activity for CVD prevention, 2) provide the first indication of whether exercise intensity reduces CVD risk via multi-level vasculature function vs. metabolic insulin action, 3) provide a rational early treatment for people with MetS. Thus, identification of the optimal drug to exercise interaction will illuminate how to develop individualized exercise/metformin prescriptions to correct vascular and ameliorate metabolic insulin resistance that attenuate/prevent progression to future diabetes and the CV morbidity and mortality.

项目总结/文摘